DESCRIPTION (From the applicant's abstract): Glutamate transport is an essential component of central glutamatergic neurotransmission; studies document an essential role for glutamate transport in the inactivation of synaptically released glutamate and the prevention of excitotoxicity. The understanding of glutamatergic neurotransmission has expanded recently with the identification of new proteins responsible for the regulation and synaptic targeting of these receptors to the synaptic cleft. Studies also suggest that glutamate transporters may be regulated and targeted to the synaptic cleft. We hypothesize that neuronal proteins exist that are responsible for the synaptic targeting and regulation of neuronal glutamate transporter subtypes; we propose to label these proteins GTRAP: glutamate transporter associated protein. In preliminary studies we have identified at least three novel and specific interacting proteins that appear to both positively and negatively modulate neuronal glutamate transporter subtypes. We will identify proteins that interact with the major intracellular domains of the two neuronal glutamate transporter subtypes: EAAT4 and EAACI (EAAT3). The aims of the studies include: 1) Identification and characterization of neuronal glutamate transporter interacting proteins. Using yeast-two hybrid screens, we will identify proteins that interact with both neuronal glutamate transporter subtypes; 2) Determine the specificity and characterization of GTRAP-transporter interaction. 3) Evaluate the cellular and ultrastructural distribution of GTRAPs and 4) to determine the physiological regulation of neuronal glutamate transporters by these novel GTRAPs.